The present invention is directed to a pharmaceutical composition containing three components. The first component is refined detoxified endotoxin (RDE) characterized as having no detectable 2-keto-3-deoxyoctanoate and having between about 350 and 475 nmoles/mg of phosphorus and between about 1700 and 2000 nmoles/mg of fatty acids. The second component is trehalose dimycolate (TDM). The third component of the composition is an acetone precipitated by-product of endotoxic glycolipids extracted with chloroform-methanol (ACP). The foregoing composition is a highly potent anti-tumor composition which is useful in the treatment of cancerous tumors in animals and in humans.
Endotoxic extracts obtained from Enterobacteriaciae including parent organisms and mutants are known. These extracts have been used for immunotherapy of various immunogenic tumors [see Peptides as Requirement for Immunotherapy of the Guinea-Pig Line-10 Tumor with Endotoxins; Ribi, et al., Cancer Immunol. Immunother, Vol. 7, pgs. 43-58 (1979) incorporated herein by reference]. However, the endotoxin extracts are known to be highly toxic and, therefore, of limited use in the treatment of cancerous tumors. Efforts have been made to "detoxify" the endotoxins while retaining their tumor regressive capacity. As shown, in Ribi, et al., chemical procedures known to detoxify endotoxins while retaining adjuvanticity, such as succinylation and phthalylation resulted in both loss of endotoxicity and tumor regressive potency. Therefore, prior art attempts to obtain an endotoxin product with high tumor regressive potency and little or no toxicity have thus far not been successful.
Acetone precipitated by-product of endotoxic glycolipids extracted with chloroform-methanol (ACP) does not possess tumor-regressive properties when used alone or in combination with trehalose dimycolate. For a more complete discussion of ACP, its properties and methods of production, reference is made to the above-mentioned Ribi, et al. publication.
It is, therefore, an object of the present invention to produce a parmaceutical composition containing a refined detoxified endotoxin product in combination with ACP and TDM which has a high tumor regressive potency without toxic side effects normally associated with endotoxin products.
It is another object of the invention to provide methods of treating animals and humans with the aforementioned composition to obtain regression or remission of tumor growths.